Can Infections Cause Alzheimer's Disease?

Abstract

Late-onset Alzheimer's disease (AD) is the most prevalent cause of dementia among older adults, yet more than a century of research has not determined why this disease develops. One prevailing hypothesis is that late-onset AD is caused by infectious pathogens, an idea widely studied in both humans and experimental animal models. This review examines the infectious AD etiology hypothesis and summarizes existing evidence associating infectious agents with AD in humans. The various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD are considered, as is the concordance between putative infectious agents and the epidemiology of AD. We searched the PubMed, Web of Science, and EBSCO databases for research articles pertaining to infections and AD and systematically reviewed the evidence linking specific infectious pathogens to AD. The evidence compiled from the literature linking AD to an infectious cause is inconclusive, but the amount of evidence suggestive of an association is too substantial to ignore. Epidemiologic, clinical, and basic science studies that could improve on current understanding of the associations between AD and infections and possibly uncover ways to control this highly prevalent and debilitating disease are suggested.

In utero exposure to the 1918 pandemic influenza in Denmark and risk of dementia

“…The hypothesized mechanism of actions for such an association includes neuroinflammation and systemic inflammation of the brain. 7,15 In conclusion, this study does not support the hypothesis that prenatal exposure to the 1918 influenza pandemic is associated with increased risk of dementia at age 62 years or older.…”

“…We are not aware of any studies that have examined the 1918 influenza pandemic's association with dementia, although other groups have more broadly studied the role infections may play in Alzheimer's disease. The hypothesized mechanism of actions for such an association includes neuroinflammation and systemic inflammation of the brain …”

“…Some investigators have hypothesized that infections may be causally associated with Alzheimer's disease, citing substantial but inconclusive evidence, with chronic infections in particular receiving more attention . We assessed whether individuals who were in utero during peaks of the 1918 influenza pandemic—a proxy for in utero influenza exposure—are at increased risk of Alzheimer's disease, vascular dementia, or other forms of dementia, compared to individuals born in the months soon before or after the pandemic peaked.…”

Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection

“…Renewed interest in possible roles for infection has been driven, in part, by recent reports of elevated levels of pathogen-derived epitopes in AD brain (Alonso et al, 2014; Harris and Harris, 2015; Pisa et al, 2015) and emerging experimental, genetic, and epidemiological data suggesting innate immune mediated inflammation propagates neurodegeneration (Griciuc et al, 2013; Heneka et al, 2015; Perez-Nievas et al, 2013). Herpes simplex virus 1 (HSV1) is the human pathogen most frequently linked to AD amyloidosis (Harris and Harris, 2015; Itzhaki, 2014; Itzhaki et al, 1997; Mawanda and Wallace, 2013). Herpesviridae proteins are reported to interact with the products of many AD susceptibility genes (Carter, 2008).…”

Helicobacter pylori infection and prevalence of stroke

“…2 The main pathological subtypes of stroke include ischemic stroke, which is most common, and hemorrhagic stroke. 6,7 It has been proposed that some infectious agents might play a role in neurological illnesses, 10 including stroke. 6,7 It has been proposed that some infectious agents might play a role in neurological illnesses, 10 including stroke.…”